This R01 application is a response to an RFA (PA-95-005) encouraging research on adolescent drug abuse (DA). An emerging, yet mixed body of evidence suggests that DA is frequently preceded by childhood attention-deficit/hyperactivity disorder (ADHD). Both DA and ADHD are major complex public health problems in and of themselves, and each appears to confer risk for further morbidity. The aim of this proposal is to test hypotheses about the co-occurrence of DA in ADHD adolescents growing up and their high-risk siblings. We are proposing a ten year, family-based, follow-up study of boys with ADHD with a focus on DA. At baseline assessment, we ascertained 140 ADHD and 120 normal control children from psychiatric and non-psychiatric settings. These groups had 454 and 368 first degree biological relatives, respectively. We have followed the probands and their siblings into early adolescence at one and four year follow-ups. Over 90 percent of the subjects ascertained at baseline were re-examined at each follow-up assessment. By the fourth year of follow-up the mean age of probands was 14.8 years. The ten-year psychiatric, psychosocial and neuropsychological follow-up of the sample was recently funded by NICHD. This proposal seeks funds that will allow us to complete a detailed assessment of DA including subjective, objective, and complementary information relevant to the development of drug DA in ADHD. Although prior follow-up studies have reported on some DA outcomes, because they have not used comprehensive assessments, the putative link between ADHD and DA is poorly understood and has been the subject of much debate. We have two main Aims: 1) To characterize DA in ADHD children growing up; and 2) To test hypotheses about measures that predict DA outcomes over a ten year period. We view the proposed extension of our work as an essential step for several reasons: First, this work will be the first systematic, prospective high risk family-based study of DA in ADHD allowing us to evaluate DA risk as it relates to the relatives of ADHD and control children; second, we will have extensive information on a well characterized group of ADHD and nonADHD children growing up spanning almost one decade; third, we did not exclude psychiatric comorbidity with ADHD at baseline permitting us to fully examine the influence of behavioral and emotional disorders within ADHD on later DA; fourth, our cases have received naturalistic treatment of their ADHD including stimulant and nonstimulant pharmacotherapy allowing us to examine the effects of stimulants on DA outcome; fifth, we will be able to examine the relationship of persistent ADHD symptoms, functionality, and wellness as they relate to later DA; and finally, since our study groups were initially collected through pediatric and psychiatric referrals, they are not biased through ascertainment for DA. Given the high prevalence of ADHD, its related comorbid disorders and its frequent persistence into adulthood, the proposed study may shed light on ADHD adolescents and young adults at highest risk for DA. Since ADHD is treatable and identifiable in early youth, this high-risk group will provide valuable information to formulate prevention interventions. Moreover, given the persistent concerns of stimulant exposure kindling later DA, this study will further clarify the impact of chronic stimulant treatment on later DA. Thus, the research, approach, and goals of this R01 application are consistent with those underscored in the RFA and by the Institute of Medicine as being of highest research priority with direct relevance to both clinical care and public health domains.